In a variety of organs or tissues, fibrosis causes reduction of parenchyma cells therein and an increase of fibrous connective tissues, eventually damaging tissue structures, causing tissue dysfunction or even organ failure. The mechanism of fibrosis, and diagnostic methods and prevention measures for fibrosis of organs or tissues have been widely studied. In prior art, considerable progress has been made in some aspects, but some key unresolved issues still exist.
U.S. Pat. Nos. 3,839,346A, 4,052,509A, 4,042,699 disclose 29 pyridone compounds having formula I as follows,
and disclose functions of the pyridone compounds of resisting inflammation, allaying fever, reducing the level of serum uric acid, relieving pain or the like, wherein 5-methyl-1-phenyl-2(1H)-pyridone (Pirfenidone) has the best activity and lower toxicity.
U.S. Pat. No. 5,310,562 discloses 5-methyl-1-phenyl-2(1H)-pyridone for the first time in 1994, that is Pirfenidone (PFD), having an anti-fibrosis biological activity; subsequently U.S. Pat. Nos. 5,518,729 and 5,716,632 disclose N-substituted-2-(1H)pyridone described as the structural formula I and N-substituted-3-(1H)pyridone having the same anti-fibrosis function. Forty-four compounds are specified, most of which are known compounds derived from U.S. Pat. No. 4,052,509; and in the compounds, R1, R2, R3, and R4 are defined as methyl groups or ethyl groups.
Pirfenidone (PFD) is proven to have effectiveness in fibrosis prevention through in vitro and animal experiments. Pirfenidone has functions of stopping or even converting ECM accumulation and preventing or reversing fibrosis and scar formation in experiments using animals with renal fibrosis and pulmonary fibrosis and in the clinical treatment of patients with idiopathic pulmonary fibrosis. (Shimizu T, Fukagawa M, Kuroda T, et al. Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy. Kidney Int, 1997,52 (Suppl 63): S239-243; Raghu G, Johnson W C, Lockhart D, et al. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone. Am J Respir Crit Care Med, 1999,159: 1061-1069). The applicant proposes a CN patent ZL02114190.8 and provides a class of pyridone compounds of the formula II.

In the structural formula II, if n=1, the substituent R is F, Br, or I; if n=2, the substituents R are F, Cl, Br, I, a saturated linear alkyl group, an oxo-saturated linear alkyl group, or a halo-saturated linear alkyl group. The substituent R is at any of the ortho-position, meta-position, and para-position on a benzene ring.
Pirfenidone came into the market in Japan in 2008 for treating indications for pulmonary fibrosis. However, Pirfenidone and its derivatives do not have high enough strength. The clinical dose of Pirfenidone achieves 2400 mg/day.
Patent publications WO 2007053685 and WO 2006122154 disclose compounds having functions of inhibiting p38 kinase, applied to treatment of fibrosis diseases and disclose the formula III;
wherein, R1-R4 each are H, an alkyl group, a substituted alkyl group, an alkenyl group, a haloalkyl group, a nitro alkyl group, a hydroxyalkyl group, an alkoxyl group, a phenyl group, a substituted phenyl group, halogen, a hydroxyl group, an alkoxyalkyl group, a carboxyl group, an alkoxycarbonyl group, etc.; X1-X5 each are H, halogen, an alkoxyl group, or a hydroxyl group.
WO 2007062167 also discloses compounds having functions of inhibiting p38 kinase and applied to treatment of various fibrosis diseases, wherein some structures are shown as follows:
Some simple substituents are provided on the benzene rings of the compounds.
CN patent 200710034357 discloses some similar compounds having the above structures with anti-fibrosis activity and a compound with the anti-fibrosis activity shown in the formula IV.

Those compounds are provided with TFM at the 5-position of the pyridone ring, thereby overcoming the disadvantages of inferior action of Pirfenidone, but the strength of those compounds is still not powerful enough.
DE patent DE4343528 reports a class of compounds having insecticidal actions for agricultural use, with the formula V as follows.

In structural formula V, A and B are substituted by various heterocyclic rings, such as furan, imidazole, pyridine and pyridone; wherein a class of compounds with the formula VI is included.

EP patents EP259048, EP367410 and EP398499 report a class of compounds having insecticidal actions for use in agriculture, with the formula VII as follows:
wherein a class of compounds having the formula VIII, in which R1 is pyridone and R10 is O or S, is included.

EP patent EP216541 reports a class of compounds having insecticidal actions for use in agriculture, with the formula IX as follows:
wherein a class of compounds with the formula X is included.

EP patent EP488220 reports a class of compounds having insecticidal actions, with the formula XI as follows:

In structures of the above-mentioned compounds, the pyridine ring and the benzene ring at the 1-position of the pyridine ring have a plurality of substituents; the compounds with complicated structures have not been reported to have the anti-fibrosis function.
DE102004027359 discloses a class of compounds capable of modulating dopamine-3 receptor and applied to treatment of Parkinson's disease and schizophrenosis;
wherein, A is a hydrocarbon chain with 4-6 atoms, having 1-2 substituted methyl groups thereon; or 1-2 carbon atoms in the carbon chain are substituted by O, C═O, S and other atoms; R1 and R2 are H, CN, NO2, halogen atom, OR5, NR6R7, C(O) NR6R7, O—C(O)NR6R7; a C1-C6 alkyl group, a C1-C6 haloalkyl group, etc.
Accordingly, compounds in the prior art have low anti-fibrosis activities and strong liposolubility as a plurality of fluorine atoms are introduced onto molecules. As a result, the compounds cannot be made into solutions because there is no highly water-soluble group in the molecule.